在2025年欧洲肺癌大会（ELCC)上，瑞士巴塞尔大学医院的肿瘤内科医生、瑞士临床癌症研究集团（SAKK）的副总裁Dr.Sacha Rothschild汇报了多中心、单组II期SAKK 16/14试验的最终分析数据（摘要189MO），并在《肿瘤瞭望》采访中进一步解读了SAKK 16/14试验结果对IIIA（N2）非小细胞肺癌（NSCLC）治疗的启示。

Dr.Rothschild：SAKK 16/14是一项针对IIIA(N2)期非小细胞肺癌患者的单组II期临床试验。这些患者接受了三个周期的新辅助化疗（顺铂和多西他赛），随后接受两个周期的抗PD-L1抗体度伐利尤单抗治疗，随后进行手术切除，术后继续接受一年度伐利尤单抗治疗。

 

SAKK 16/14既往已发表的研究结果显示，该试验达到了1年无事件生存期（EFS）这一主要终点。1年EFS率从早期单纯化疗试验中的约50%提高到本试验的73.4%。我们目前已在巴黎的ELCC大会上公布了最终分析结果，中位随访期为6年。经过6年的中位随访，中位EFS为4年，中位总生存期（OS）尚未达到，病理学完全缓解率（pCR）为18.2%。主要病理缓解（MPR，定义为切除标本中残存活肿瘤细胞≤10%）的发生率超过60%。此外，pCR和MPR是预后的主要预测因素。pCR患者的中位EFS在中位随访6年后仍未达到。

 

SAKK 16/14研究：无事件生存和总生存

 

SAKK 16/14研究：MPR和pCR患者的EFS和OS

 

Dr.Rothschild:SAKK 16/14 was a single arm phase II trial for patients with stage IIIA(N2）NSCLC.These patients were treated with three cycles of neoadjuvant chemotherapy，cisplatin and docetaxel，followed by two cycles of the anti-PD-L1 antibody，durvalumab，followed by resection，and then one year of post-operative durvalumab.What we have already published is that the primary endpoint of one-year event-free survival was reached.One-year event-free survival was increased from 50%in our earlier trial with chemotherapy alone to 73%in this trial.We have now presented at ELCC in Paris，the final analysis with a median follow-up of 6 years.After a median follow-up of 6 years，we have a median event-free survival of 4 years，and a median overall survival that has not yet been reached.The rate of pathologic complete remission in this trial was 18%.The rate of major pathologic remission defined as<10%viable tumor cells in the resection specimen，was>60%.Also，pCR and MPR are major predictors of outcome.Patients with pCR have a median event-free survival that has not been reached after a median follow-up now of 6 years.

 

Dr.Rothschild：目前我们发现，PD-L1表达是疗效的预测指标，因此PD-L1较高表达（定义为免疫组化[IHC]检测>25%）的患者有更高的机会获得缓解，实现更高的pCR和MPR，以及更长的无事件生存期。所以，PD-L1是已确定的预测指标，目前还没有其他预测标志物。

 

我们开展了非常全面的转化研究项目与SAKK 16/14临床试验同步进行，因此我们拥有来自初始活检和切除标本的肿瘤组织，并进行了特定时间点的血样分析，我们希望找到更多更好的预测标志物来预测新辅助或围手术期免疫治疗的疗效。

 

Dr.Rothschild:What we see so far is that PD-L1 expression is a predictor of response，so patients with high PD-L1 expression（defined as an IHC level>25%）have a higher chance to respond and achieve higher pCR and MPR，and also a longer event-free survival.So，PD-L1 is a predictor.Other than that，we don’t yet have any other predictive markers.

 

However，we had a very comprehensive translational research program going along with this clinical trial，so we have tumor tissue from the initial biopsies and from the resection specimen，we had defined time point blood sample analyses，and we hope to find more and better predictive markers for a response to neoadjuvant or perioperative immunotherapy.

Dr.Rothschild：我认为今年ELCC会议的一些研究非常引人注目，报道了很多重要的试验。

 

EGFR突变NSCLC治疗：MARIPOSA试验的总生存期分析显示，埃万妥单抗+兰泽替尼联合治疗将改变EGFR突变阳性NSCLC的治疗格局。我们目前还不确定是否需要将埃万妥单抗+兰泽替尼作为一线治疗，因为虽然其带来总生存期改善，但也显著增加了毒性。COCOON试验结果（摘要10MO）显示，在埃万妥单抗联合兰泽替尼一线治疗EGFR突变晚期NSCLC时，采用预防性强化皮肤管理方案较标准皮肤管理使患者对治疗有更好的耐受性（可显著降低皮肤不良事件发生率和严重程度）。

 

KRAS靶向治疗：2025 ELCC在KRAS G12C突变阳性NSCLC患者中发布了许多有趣的结果，例如，对于PD-L1高表达（PD-L1≥50%）的KRAS G12C突变阳性晚期/转移性NSCLC患者，Adagrasib联合帕博利珠单抗一线治疗实现了令人振奋的27.7个月PFS，虽然增加了毒性，但证明将免疫检查点抑制剂与靶向疗法相结合是一种可行的方案（摘要5MO）。另一种KRAS G12C抑制剂氟泽雷塞与西妥昔单抗联合用于KRAS G12C突变NSCLC一线治疗显示出非常令人瞩目的总体缓解率（KROCUS研究；摘要LBA1）。

 

ELCC 2025无疑是一场重要的会议，我们看到了许多重要的研究成果，希望这些成果能够改变治疗格局，改善患者的预后。

 

Dr.Rothschild:An important question.I think we are seeing a very interesting ELCC this year with many important trials.

 

I would like to highlight some of the abstracts for EGFR mutation-positive disease.Here we have seen the overall survival analysis for the MARIPOSA trial.This is a treatment landscape that will change in EGFR mutation-positive disease with the combination of amivantamab and lazertinib.We don’t know yet whether it needs to be given in frontline.Although we have seen the overall survival results，it is also a toxic regimen.We have seen the COCOON trial showing us that probably tolerability is better with pre-emptive therapy and prophylactic treatment of patients on amivantamab.I would also like to mention the KRAS field.We have seen a lot of interesting results for KRAS G12C mutation-positive NSCLC patients，showing，for example，that adagrasib can be combined with pembrolizumab in patients with high PD-L1 expression in KRAS mutation-positive disease.This leads to a very intriguing progression-free survival rate in the first-line setting of 27 months.It is also a toxic therapy，but this is certainly one way to go–to combine checkpoint inhibitors with targeted therapies.We have seen another KRAS G12C inhibitor combined with cetuximab in the frontline setting showing a very intriguing overall response rate.

 

So，this is definitely an important conference，and we have seen a lot of important results that hopefully will change out treatment landscape and will improve outcomes in our patients.

 

参考文献1.Rothschild S，et al.Perioperative Durvalumab in Addition to Neoadjuvant Chemotherapy in Patients With Stage IIIA(N2）Non-Small-Cell Lung Cancer-Final analysis of the trial SAKK 16/14.2025 ELCC，189MO.

 

《肿瘤瞭望》在ELCC现场报道